The outlook for patients with lung cancer has remained dismal over the last 20 years. While new treatment paradigms have emerged, they are uniformly disappointing in altering the course of patients with advanced lung cancer which is the case with the majority of the patients facing this diagnosis. With this situation, a logical approach is to try to improve the early detection of this disease. Traditional approaches have focused on imaging and bronchoscopy to achieve this aim. Novel approaches being developed aim at developing a blood test for the diagnosis of lung cancer. Most of these approaches use proteins because of their stability in blood. Nucleic acids have not been proven to be useful because of their instability in blood. Recent evidence points to the stability of small (18 -22 nt) tissue and disease specific RNA known as microRNA in serum and plasma. Therefore, these molecules have the potential to serve as biomarkers. A particular advantage of using these molecules over proteins is the availability of high throughput microarray technology to measure their levels of expression. This proposal aims to study expression patterns of microRNA in the blood of patients with lung cancer and compare them to those in patients at high risk of developing lung cancer, but have not done so yet. The first phase of the study will look at these expression patterns in both serum and plasma to determine which substrate is better. The second phase of the study will attempt to identify a microRNA expression profile capable of separating the two comparison populations. The third phase of the trial will validate such a profile in an independent set of patients to determine its accuracy at diagnosis. Identification of such a profile can not only serve as a diagnostic tool, but can potentially serve as a biomarker for the lung cancer disease state.